1. Technical Field
This invention relates to a means for promoting the neutralization reaction between particulate calcium carbonate-derived products and ionized phosphate and to a process for the preparation of a modified calcium carbonate reactant.
2. Background Art
Calcium carbonate, in the form of limestone or in the form of pulverized shells from crustaceans, is a basic material used for the neutralization of acids. Calcium carbonate is a generally non-toxic material and the residues from its use provide no particular hazards for disposal.
In the medical fields, excessive acids present in the stomach and small intestine have been identified as a cause for pain and may be directly involved in either the formation of ulcers or the irritation thereof. Commercially available antacids typically contain calcium carbonate, magnesium hydroxide, aluminum hydroxide and combinations thereof. Unavoidable side effects from the use of these compounds include effects on bowel movements from magnesium hydroxide and aluminum hydroxide, magnesium tending to cause diarrhea and aluminum hydroxide causing constipation. Calcium compounds have the unfortunate side effect that a feedback mechanism results in the delayed generation of increased amounts of stomach acids. Sodium compounds, which are also available as antacids, are generally not preferred because the increased amount of sodium is contraindicated for persons on restricted diets to control hypertension and heart or kidney diseases. As a general rule, commercial antacids contain only trace amounts of sodium.
Serum phosphate levels serve an important regulatory function in mammals. Hyperphosphatemia is associated with the development of secondary hyperparathyroidism and renal osteodystrophy in patents with uremia. While the exact control mechanism is not clear, hyperphosphatemia appears to be related to calcium malabsorption which is commonly observed in patients with advanced renal insufficiency. Since serum calcium levels control the release of parathyroid hormone, if hyperphosphatemia can be avoided secondary hyperparathyroidism can be prevented (See Slatopolsky et al., N. Engl. J. Med., 315, 157 (1986).
One mode of treatment for patients with hyperphosphatemia is the use of phosphate binders that contain aluminum. While this mode of treatment is generally successful in the short term, the accumulation of aluminum over an extended period of time results in the development of osteomalacia. Slatopolsky et al have shown that calcium carbonate, in particular Os-Cal.RTM., a commercially available calcium supplement which is derived from oyster shells, can be effective in the control of hyperphosphateima.
The use of a calcium carbonate compound as a phosphate binder, in place of aluminum containing compounds, offers obvious advantages but its utility is limited by the recognized hazard that metastatic calcification will occur in patients undergoing long term therapy. It is advisable, therefore, to limit the amount of calcium provided in a calcium carbonate-based phosphate binder.
A major commercial use for calcium carbonate is the treatment of acidic waters and gases for environmental protection. Granulated or pulverized limestone is typically the calcium carbonate source and numerous processes have been disclosed in the prior art to enhance the effectiveness of calcium carbonate for this purpose (see U.S. Pat. No. 4,629,130).
A particular concern, from an environmental standpoint, is the presence of phosphate in lakes and rivers. Excess phosphate causes algae blooms, which result in oxygen depletion of the water and the death of other organisms present. For this reason, the phosphate discharges should be controlled wherever possible but control is, at best, difficult. Conventional sewage treatment processes remove relatively small percentages of the phosphate entering the system and run-off from agricultural lands is rarely subject to any treatment.
It is known that the rate and extent of reaction between a given quantity of phosphate ion and a given quantity of particulate calcium carbonate is dependent on the physical capability of each phosphate ion to contact a calcium carbonate molecule in solution or at a surface. The efficiency of the reaction between phosphate ion and particulate calcium carbonate is impeded by the formation of the relatively insoluble tricalcium phosphate on the external surfaces of the calcium carbonate particle involved. As a result, when calcium carbonate is used to remove phosphate ions, an excess of calcium carbonate is typically required. In medical applications, the presence of excess calcium is undesirable. For non-medical uses the inefficiency of the reaction results in increased costs for treatment.
It is one object of this invention to provide a modified product comprising calcium carbonate having a more efficient neutralization reactivity towards phosphate ion when compared to the unmodified calcium carbonate conventionally used. It is a further object of this invention to provide a calcium carbonate comprising product for medical purposes having a significantly greater capacity, on a weight basis, for neutralizing phosphate ion in the presence of chloride ion as compared to the calcium carbonate used to prepare the product. A further objective is to provide a calcium carbonate comprising product suitable for inclusion in antacid preparations for the control of excess acid in the intestinal tract. A further objective is to provide a calcium carbonate comprising composition useful, when administered per os to lower blood serum phosphate levels and which also may be used to control serum calcium levels.
A further objective of this invention is to provide calcium carbonate and calcium fluoride containing compositions, having solubility characteristics suitable for ingestion, to supply fluoride ion and calcium ion for therapeutic purposes. A still further object is to provide calcium carbonate containing products having added fluoride suitable, when used in admixture with Vitamin D and other adjuvants to be utilized in the manufacture of calcium carbonate containing therapeutic agents. (A commercially available calcium carbonate product containing calcium and Vitamin D in the ratio of 250 mg Ca to 125 USP units of Vitamin D is Os-Cal.RTM., manufactured by Marion Laboratories, Kansas City, Mo. 64137). A further objective of this invention is to provide a fluoride ion containing mild abrasive suitable for use in dentifrices.
It is a further objective of this invention to provide an improved method for the removal of phosphate ion from rivers, lakes and streams, and in industrial process, by providing a calcium carbonate containing product having a more efficient neutralization reactivity toward phosphate ion and having a significantly greater capacity, on a weight basis for neutralizing phosphate ion. A further objective is to provide enhanced reactivity in the presence of ubiquitous environmental contaminants such as chloride ion.